Colorectal Cancer

Colorectal cancer is the second leading cause of cancer related death in the United States. Approximately 160,000 new cases were diagnosed in 1996, and an estimated 60,000 individuals died from their disease. Treated surgically and with curative intent, one-third will develop tumor recurrence and die of metastatic disease. During the 1970's, studies reviewing outcome data and patterns of failure have identified subsets of patients at risk for local or systemic recurrence. These reports lead to the development of adjuvant therapies using external-beam irradiation, 5-FU based chemotherapy and combinations of these treatments. Adjuvant therapy refers to the administration of chemotherapy and or radiation therapy after curative surgery to eradicate microscopic disease responsible for these recurrences.

Patients at high risk of relapse are identified by pathologic stage as determined at surgery following examination of the resected specimen. The Astler-Coller modification of the Dukes system, and the TNM (tumor-node-metastases) classification of the American Joint Committee of Cancer are the staging systems most commonly used. Most patients with early-stage colon cancer (stage A and B1) are cured by surgical resection alone. Tumor invasion through the bowel wall (stage B2-3) results in a survival of 70%, while involvement of lymph nodes (stage C1-3) decreases survival to 25% with increasing number of lymph node metastases. Bowel perforation, obstruction and adherence or invasion of adjacent organs increases the risk of recurrence. Rectal cancer and colon cancer have different natural histories due to the anatomical location of the tumor. The rectum is a retroperitoneal organ in the bony pelvis adjacent to the bladder. It is difficult for surgeons to achieve wide radial margins in this area. Consequently, there is a greater incidence of local failure associated with rectal cancer, compared to extrapelvic colon cancer. Adjuvant therapies, therefore, will differ depending on the location of the tumor.

Approximately 25-30% of patients undergoing potentially curative surgery for rectal cancer will experience a locoregional failure. Additional local therapy consisting of preoperative or postoperative radiation therapy is often needed. Radiation therapy directed to the pelvis, in conjunction with chemotherapy, is recommended following resection of rectal cancers that extend through the bowel wall, or were associated with positive lymph nodes. In addition, there are circumstances when radiation therapy is recommended following surgical resection of extrapelvic colon cancers. The reduction of local failure by radiation therapy impacts minimally on survival requiring the addition of 5FU based chemotherapy to irradicate the distant sites of metastases. The Gastrointestinal Tumor Study Group (GITSG) and the North Central Cancer Treatment Group (NCCTG) have demonstrated that local relapse and overall survival were improved in the combined modality group. Studies are ongoing to determine the optimal adjuvant treatment regimen.

Advances in adjuvant therapies for rectal cancer include pilot trials and ongoing research exploring preoperative radiation therapy with and without preoperative chemotherapy. Preoperative combined modality treatment results in tumor downstaging and improved resectability rates. Improvements in staging technologies, such as the endorectal ultrasound, provide for nonoperative staging, facilitating our ability to select patients for preoperative therapies. In patients with clinically resectable rectal cancer there is increased interest in combining radiation therapy and local surgery to preserve anorectal sphincter function. A variety of innovative sphincter sparing operations are being developed. Suitable patients must be selected reviewing resectability, tumor histology, tumor size, location, and mobility. The technical expertise of the radiation oncologist and operating surgeon will dictate the treatment approach.

The physicians of Valley Radiotherapy Associates Medical Group endorse this approach and are committed to individualizing treatment strategies to achieve maximal cure rates with preservation of function. Multi-specialty integration of physicians including pathologists, radiologists, radiation oncologists, surgeons and medical oncologists will ensure that suitable patients are offered the alternative approaches. Preoperative radiation therapy followed by coloanal anastomosis, local excision with postoperative radiation therapy, or radiation therapy alone are potential options. The clinical situation dictates the approach used.

Toxicity resulting from adjuvant therapies for colorectal cancer include altered bowel function. Diarrhea, abdominal cramping, urinary urgency and frequency can occur during radiation therapy. Appropriate supportive and therapeutic measures are utilized as necessary. When radiation therapy is combined with chemotherapy, low blood counts may result in interruption of therapy until adequate recovery has occurred. Late complications such as obstruction, perforation, or fistulas occur at a rate similar to that after surgery alone and are less than 5%.

References:

1. American Joint Committee on Cancer: Colon and rectum. In: Manual for Staging of Cancer, edited by O Beahrs, D. Henson, R. Hutter, et al, Philadelphia, JB Lippincott, 1988, pp 75-80.

2. Vokes E., Weichselbaum R.: Concomitant chemoradiotherapy: rationale and clinical experience in patients with solid tumors. J. Clin. Oncol. 8:911-920, 1990.

3. Gastrointestinal Tumor Study Group: Survival after postoperative combination treatment of rectal cancer. N. Engl. J. Med. 315: 1294-1295, 1986.

4. Minsky B.D..: Preoperative combined modality treatment for colorectal cancer. Oncology 8:53-68, 1994.